This invention relates to compositions which include a ruthenium(III) complex and a heterocycle and also to their application as medicaments for the treatment of cancer illnesses.
The possible applicability of ruthenium complexes in the treatment of cancer illnesses has been discussed by M. J. Clarke, ACS Symp. Ser. 140 (1980) 157-180.
Complex compounds of trivalent ruthenium with pyrazol and imidazol have been described by F. Kralik et al., Collection Czechoslov. Chem. Commun. 26 (1961) 1298 and by B. K. Keppler et al., Inorg. Chem., 26 (1987) 4366-4370.
Furthermore, ruthenium(III) complexes with indazol and dimethyl sulfoxide have been investigated by B. K. Keppler et al., Anticancer Res., 9 (1989) 761-766, G. Mestroni et al., J. Am. Chem. Soc. 111 (1989) 7068-7071 and G. Mestroni et al., Inorg. Chem., 34 (1995) 4722-4734.
The tumor-inhibiting properties of ruthenium(III) complexes with a basic heterocycle, such as indazol, are also described in Eur. J. Inorg. Chem. 1999, 9, pp. 1551-1555, Met.-Based Drugs 1994, 1 (2-3), pp. 145-150 and J. Cancer Res. Clin. Oncol. 1992, 118(3), pp. 195-2000.
In the U.S. Pat. No. 4,843,069 medicaments are described which contain ruthenium(III) complexes with a monocyclic or multi-cyclic basic heterocycle. The complexes are suitable for cancer therapy, but are difficult to dissolve in water and are therefore not lyophilisable.
To avoid this disadvantage, WO97/36595 discloses ruthenium(III) complexes with an alkali metal cation or with ammonia which are easily soluble in water and which are also effective in the treatment of cancer illnesses. However, these compounds have the disadvantage that they exhibit a lower effectiveness than ruthenium complexes according to U.S. Pat. No. 4,843,069.